Anti-apoptotic use of human glutaminyl-tRNA synthetase with two consecutive pro-apoptotic mediators

Abstract

Aminoacyl-tRNA synthetases are the enzymes catalyzing ligation of their cognate amino acids and tRNAs. Human glutaminyl-tRNA synthetase (QRS) consists of the unique N-terminal extension (236 aa) and the C-terminal catalytic domain (539 aa). Here, we found that the N- and C-domains of QRS interacted with pro-apoptotic mediator, Daxx, and its downstream kinase, ASK1 (apoptosis signal-regulating kinase), respectively. The experimental results suggest that QRS may inhibit the ASK1 activity via two different ways. First, its C-terminal domain made direct inhibitory interaction with ASK1. Second, it inhibited the pro-apoptotic interaction between Daxx and ASK1. QRS also blocked the Daxx-ASK1 mediated apoptosis. Thus, QRS is not only an enzyme for protein synthesis but also plays a regulatory role in apoptosis

What is claimed is:  
     
       1. A method for regulating apoptosis by a cell, comprising introducing into said cell a human glutaminyl-tRNA synthetase (QRS), wherein said synthetase consists essentially of a N-terminal extension domain and a C-terminal catalytic domain and wherein regulation of apoptosis is effected by interaction of said human glutaminyl-tRNA synthetase with a pro-apoptotic mediator and apoptosis signal-regulating kinase in said cell. 
     
     
       2. The method according to  claim 1 , wherein said N-terminal extension domain interacts with Daxx, thereby effecting inhibitory regulation. 
     
     
       3. The method of  claim 1 , said C-terminal catalytic domain interacts with ASK1, thereby effecting inhibitory regulation. 
     
     
       4. The method of  claim 1 , wherein said C-terminal catalytic domain blocks interaction between Daxx and ASK1, thereby effecting inhibitory regulation.